Research/Clinical Interest

The role of white matter changes in aging and Alzheimer's disease
The overall goal of my research is to elucidate the role of white matter pathology in the development of age-related cognitive deficits. Currently, our studies have shown two significant changes in white matter pathology with aging malfunctioning of oligodendrocytes and demyelination of axons. Further, cholesterol trafficking is disturbed early in the aging process in the white matter, specifically in astrocytes, and since astrocytes are the main source of cholesterol in the brain, this likely leads to changes in the myelin sheath. Together these changes will lead to a “functional” disconnection in the brain leading to cognitive disturbances. We are investigating these changes in oligodendrocyte dysfunction in the white matter, and the development of cognitive impairments, using a combination of behavioral, immunohistochemical and molecular biology approaches. Furthermore, we have recently discovered changes in the expression of epigenetic markers with aging, i.e., changes in HDACs and DNMTs in the white matter. This novel discovery has lead to potential new therapies for age-related white matter pathology. A second research interest is the role of vascular pathology in Alzheimer’s disease, specifically hypertension and the relation between white matter infarcts and AD pathology. While clinical data strongly suggest that small infarcts contribute significantly to cognitive decline, the causal relationship is still not clearly defined. Our studies have shown that small ischemic infarcts both increase Aß deposition and decrease cognition. Furthermore, we have found that white matter infarcts (compared to grey matter infarcts) have a significantly worse outcome. Currently we are focusing on the role of hypertension in age-related cerebral dysfunction and Alzheimer’s disease. Some of my current studies include the use of therapeutic agents (i.e., amyloid β binding peptides) that may be promising in the alleviation or delay of age-related neural and cognitive changes. Further, currently, we are investigating the role of obesity, and/or caloric restriction and hunger in the development of cognitive deficits in AD.